Study Reveals Prognostic Biometrics for Uveal Melanoma

Pipetting sample into a tube ready for genetic testing. Results of a DNA test are at right.
Combining gene expression profile, largest basal diameter optimizes prediction of early metastasis-free survival in uveal melanoma.

Both gene expression profile (GEP) and largest basal diameter (LBD) provided researchers the ability to separate patients with uveal melanoma into 4 “easy-to-use” prognostic groups (resembling a model that combines the American Joint Committee on Cancer stage with GEP), according to a study published in the British Journal of Ophthalmology

The study included 348 patients (mean age 60 years ± 14 years) who underwent plaque brachytherapy or enucleation for uveal melanoma that involved the choroid or ciliary body, or both, from 2012 to 2019, with a follow-up of a mean of 40 months ± 26 months (3.3 ± 2.2 years). 

Investigators found that, on multivariate analysis, LBD larger than 12 mm remained a significant independent predictor of metastasis for class 1 (HR 21.90; 95% CI 2.69 to 178.02; P =.004) and class 2 (HR 2.45; 95% CI, 1.03 to 5.83; P =.04) tumors. 

The team then created 4 prognostic groups: group 1 (class 1, LBD smaller than 12 mm), group 2 (class 1, LBD at least 12 mm), group 3 (class 2, LBD smaller than 12 mm), and group 4 (class 2, LBD at least 12 mm). They used life tables to calculate 3-year and 5-year metastasis-free survival: group 1 (98% and 98%), group 2 (86% and 86%), group 3 (81% and 62%), and group 4 (54% and 47%). 

When compared with the reference category (group 1), the Cox proportional hazard model demonstrated a significant worsening of survival for each progressive category (group 2 (HR 21.59; P =.004), group 3 (HR 47.12, P <.001), and group 4 (HR 114.24; P <.001)). 

“In our dataset, the four-category Cox model performed poorer compared with the American Joint Committee on Cancer (AJCC) and gene expression profile (AJCC+GEP) in the Akaike’s information criteria (AIC) (297 vs 291), fit better with the Bayesian information criteria (BIC) (309 vs 313) and performed similarly with the Harrel’s C (0.86 (95% CI 0.80 to 0.91) vs 0.89 (0.84 to 0.94), respectively),” according to the study.

Limitations of the study include the small number of outcome events — 41 patients developed metastasis when the GEP-alone predicted that 54 patients would have developed it over the study’s follow-up. 

“The lower-than-expected rate of metastasis in this cohort of patients is likely due to the importance of tumor size and the relatively small tumors included in our study compared with the studies validating GEP,” according to the researchers. “As the majority of our cohort was comprised of stage I (47%) and stage II (41%) lesions, our overall metastatic rate of 12% appears to be in keeping with previously published series”. 

More follow-up time is needed to determine who might go on to develop metastasis. “Our conclusions regarding the comparison of this four-group system to AJCC should be interpreted in the context of our study size and number of metastasis. Therefore, further studies are required to validate our findings on an independent dataset.”


Roelofs KA, Grewal P, Lapere S, et al. Optimising prediction of early metastasis-free survival in uveal melanoma using a four-category model incorporating gene expression profile and tumour size. Br J Ophthalmol. Published online February 15, 2021. doi:10.1136/bjophthalmol-2020-317714